Population-level predictors of sexually transmitted infection rate changes in Missouri: an ecological study

Background Sexually transmitted infection rates continue to increase across the US, further developing health disparities and economic burdens of disease, especially as migration occurs. In this study, we aim to assess the relationship between STI rates and population-level variables from 2008 to 2017 at the county level in Missouri. Methods Two data sources were used: STI rates of chlamydia, gonorrhea, syphilis, HIV reported to Missouri DHSS and ACS 1-year county population estimates. Linear regression models and ANOVA tests were conducted in SPSS for each STI from year-to-year and 2008–2017. Covariates included in the analyzes were county-level income, employment rate, race, ethnicity, age, and percent poverty. Further, Akaike Information Criterion tests were performed to indicate the best predictor models and averaged standardized beta values. Results Significant relationships among STI rates and population growth were identified. Chlamydia, syphilis, and HIV were positively associated with population growth from 2008 to 2017 (β = 0.15; β = 0.01; β = 0.05, respectively). Gonorrhea was negatively associated with population growth (β = − 0.02) but positively associated with unemployment rates (β = 0.01) highlighting the need to address population growth, as well as other variables in a population. Conclusions There seems to be a positive relationship among population change and rates of STIs. As populations change, rates of STIs change. Moving forward, quantitative work should be conducted in various states and the nation to understand this relationship in different contexts. Future studies should be qualitative word focused on county health departments and community health improvement plans. Lastly, public policy should be implemented to buffer the impact of migration on health outcomes.

Latinos, are not being adequately reached, especially in the South [4].
There are serious implications if infected individuals go unscreened and untreated after contracting STIs. The reasons for not seeking diagnosis and treatment can be complex. Marginalized ethnicities, individuals that may experience racism, homophobia, and xenophobic interactions, and impoverished populations, have the lowest access to healthcare and screening tests, placing them at high risk of acquiring STIs [5]. Drug use also increases risk of STI contraction, along with unplanned pregnancies [6]. More specifically, methamphetamine use, a known problem within Missouri, increases libido and risky sex among its users [6]. Finally, group sex or sex with multiple partners can increase risk of transmission [7].
Some STIs can manifest asymptomatically more so in women and cause them to go unscreened and untreated for longer than men who typically develop symptoms faster and more noticeably [8]. For this reason, women often suffer more severe, long-term complications from STIs, some including chronic pelvic pain, ectopic pregnancies, and infertility [8].
Between screening, treatment, and long-term management of STIs, the estimated financial burden in the United States is around $15.6 billion [9]. Chlamydia and gonorrhea account for $516.7 million and $162.2 million respectively, while syphilis accounts for $39.3 million, and HIV for $12.6 billion. HIV accounts for 81% of the total annual cost of STIs in the US. The overall increase in STI cases has not been limited to a single social group, age group, gender, or socioeconomic class [7]. These costs may change as STIs shift, such as the emergence of multi-drug resistant gonorrhea [10]. Although data over the cost of STIs within Missouri is unknown, in 2016, the CDC provided $6.8 million in funding specific for HIV/ Acquired Immunodeficiency Syndrome (AIDS) prevention and treatment and an additional $2.2 million in funding specific for other STIs. These values may be subject to change as multi-drug resistant gonorrhea becomes more prevalent [10,11]. Antibiotic resistant gonorrhea has the potential to become an incurable, chronic disease resulting in disability and death in a previously easily curable infection, highlighting the need to research and intervene in STIs at a population-level now [12].
It is known that increased levels of unemployment can cause lowered income for individuals and families [13]. Increased poverty levels have been linked to increased practice of risky sexual behaviors, like using a condom inconsistently or never, not using oral contraceptives, or other forms of birth control, while also having more sexual partners and 'one-night stands' [13]. These behaviors increase risk of both encountering and contracting an STI [13]. Here, it can be seen that population-level variables, or macro effects, can effect STI rates and spread as populations continue to change and encounter different situations.
Social epidemiology, a research methodology and theoretical framework that focuses on social determinants, practices, and health outcomes, provides an appropriate framework to address the factors that impact STI rates. Macro effects on disease and STI transmission are often ignored and instead the focus is put on individual risk factors [7]. Social epidemiology defines three levels to the spread of STIs throughout society: 1) individual components, 2) social components, and 3) structural components [14]. Individual components involve biological susceptibility and risky behaviors. Social components involve networks, communities, and how disease diffuses across populations [14]. The structural components are grouped into 1) cultural context, 2) social networks, 3) neighborhood effects, and 4) social capital. Social epidemiology can be used as a lens to understand the impact of population change and STI rates within a state. Social epidemiology lacks the insight of an individualized point of view on STIs, but the majority of data focuses on individual trends [7]. It instead provides insight into largescale trends affecting many with STIs, where data may be less extensive but equally compelling due to the vast amount of individuals it can then reach [7].
Given the social complexity and financial cost of STIs, it becomes critical to monitor changing rates of these infections not only throughout static populations but also as moving populations change proportions of age, gender, ethnicity, and sexuality. With these changing dynamics, estimated risks of STI transmission fluctuate as different groups have different risk factors surrounding STIs [7]. As populations grow and move, the incidence of STIs is expected to grow, showing the importance of population-level predictors alongside individual interventions. Moving, changing populations face problems of isolation and loneliness after relocating [12]. It has been observed that moving populations typically experience a higher risk of contracting STIs [15]. Characteristics of a moving population include the social disruption that accompanies geographic relocation and a lack of access to health resources [15]. STIs have remained persistent within society, in part, due to failure to contact trace all sexual partners of STI patients [9]. This is possibly due to geographic or networking barriers, consistent with a moving population. Young people and those seeking secondary education most often have to relocate, particularly from rural to urban areas [16]. In the past, the urban population of the world has increased much more quickly than those of the rural population [12]. This is expected to remain the trend into the future as the United Nations expects the world population to increase to 9.1 billion by 2100 with urban population continuing to increase in population size, and rural populations moving more towards urban areas [12]. Urban populations were considered the only "high-risk" areas for STI spread in the past, but new pockets of widespread infection in less densely populated areas have begun to form [8]. In this study, we analyze the relationship among common STIs and population change at the county level in the state of Missouri from 2008 to 2017.

Methods
This study is an ecological study with the entire population of Missouri included in the analysis. Data was excluded if it did not address STI rates or populationlevel variables for the state of Missouri. A sample size calculation was not needed as data was reported and analyzed regarding the entire state of Missouri. To find the complete population count for Missouri, the Federal State Cooperative Program for Population Estimates, National Center for Health Statistics, and US Census Bureau were used. In order to understand the demographics of the Missouri population, data was taken from the Missouri Information for Community Assessment (MICA) by the Missouri Department of Health and Senior Services (DHSS) regarding county-level data on individuals aged between 15 and 44, sex, race, and ethnicity for each year between 2008 and 2017 [17]. Data on county-level households living below the poverty level was recorded from the Small Area Income and Poverty Estimates (SAIPE) Program through the Census Bureau [18].
Chlamydia, gonorrhea, and syphilis are all diseases that are required to be reported to the county health department with each new case. Each case that is reported to a county health department is required to be reported to the state health department [19]. The state health department then reports new cases of chlamydia, gonorrhea, and syphilis for each month and year. Incidence of the three STIs: chlamydia, gonorrhea, and syphilis were then compiled from the Missouri DHSS for each year between 2008 and 2017 [19]. Incidence and prevalence of HIV was obtained through Geographic Information System (GIS) programming by the Centers for Disease Control and Prevention from the years 2008-2016 [20]. At the time of this analysis, 2017 data were not available to the public. All data were exported into Excel and SPSS (version  Table 1. Using population change as the independent variable, unadjusted multi-variate linear regression models were conducted with HIV prevalence and incidence of HIV, syphilis, gonorrhea, and chlamydia as dependent variable year-to-year and from 2008 to 2017 in SPSS (version 24).
In SPSS, further analysis used population change as an independent variable to produce unadjusted multivariate linear regression models with HIV prevalence and incidence, syphilis, gonorrhea, and chlamydia as dependent variables. These models showed the relationship from year-to-year and from 2008 to 2017 and preliminary findings showed a positive relationship between population change and STI rate changes.
Finally, Akaike Information Criterion (AIC) tests were conducted to define a best change predictor model for STI rates [21,22]. The Akaike information criterion is a statistical test used to find the best change predictor models in datasets when multiple possible variables are being examined. Use of the AIC as a model fit test has been used previously in research surrounding STIs propelling it to be selected for further analysis in this study in order to find the best fit predictor model for the change in STI rates over the 10-year timeframe [23]. These variable combinations are considered significant and equally qualified predictor models if the ΔAIC, or change in Akaike Information Criterion, value is below two. Of those found to be similarly qualified change predictor models, the weights, or w i , and R 2 values can then be further calculated to predict the likelihood of the significant models being classified as the best change predictor model in the dataset [24]. All models predicted to be of best fit gave similar w i and R 2 values, showing that each model can be a good predictor in the future change of STIs. Note that a small alteration was made to the analysis with HIV being reported as total cases for the years of 2008 and 2017, instead of the two distinctions of incidence and prevalence to allow for a larger, more significant sample size. Table 1 presents the percent change of study variables from 2008 to 2017, including: race/ethnicity, average household income, average unemployment rate, and population size. Most counties showed a negative percent change in white individuals and average unemployment rates and a positive percent change in African American individuals and Latinx individuals. Table 2 shows the percent change in STIs from 2008 to 2017. Most counties showed considerable percent increases in chlamydia, gonorrhea, and syphilis. The counties show mixed positive and negative percent changes regarding HIV, possibly due to the limited sample sizes and a focus on HIV prevention. Table 3 shows the results of the linear regression among STIs and population change between 2008 and 2017. The association between population change and chlamydia (β = 0.60, p < 0.05), gonorrhea (β = 0.50, p < 0.05) and syphilis (β = 0.2, p < 0.05) showed a significant positive association. HIV diagnoses from 2015 to 2016 was positively associated with population change (β = 0.30, p < 0.05). HIV prevalence showed a similar positive association (β =0.03, p < 0.05). As populations increase or decrease in counties in Missouri, rates of STIs increase and decrease too. Table 4 displays the results from the Akaike information criterion test (AIC) with the significant change predictors bolded for each STI. Table 5

Discussion
This study identified several relationships between common STI rates and population-level variables across Missouri at the county level. A positive relationship exists between population change and STI rates. This study also shows that population growth and size are as integral to predicting the change in STIs as other structural-level functions, like income and unemployment. As populations change, rates of STIs change.
Population growth and total HIV cases showed a positive relationship through model average standardized beta values (β = 0.05205). If we extrapolate these results to predict future cases, we would expect 52 newly-diagnosed or existing-when-moving-into-the-county cases of HIV if the population of a county grew by 1000 people. The lifetime cost of a single case of HIV is estimated as $304,500 in medical expenses [9]. An increase in 52 new cases of HIV would cost a county $15.83 million more in healthcare expenditure.   Population growth was positively associated with chlamydia such that an increase of 152 cases may occur per additional 1000 people (β = 0.15206). This adds $29,550 total in additional costs, if the cases are treated successfully after initial infection [9]. Costs increase to $3.5 million total when considering sequalae costs in asymptomatic cases. A large cost disparity exists between male and female cases, highlighting the need to intervene on those infected before chlamydia can spread in a county [9].
Population growth was positively associated with syphilis such that an increase of 7 cases may occur per additional 1000 people. This adds $4.963 in additional costs per 1000 people for treatment of syphilis (β = 0.00664) [9]. Costs increase significantly and vary in reflection to the syphilis progression. The cheapest option after syphilis contraction, is immediate treatment before possible disease progression.
Population growth was negatively associated with gonorrhea such that a decrease in 27 cases may occur per additional 1000 people (β = − 0.02705). Interestingly, unemployment was positively associated with gonorrhea such that an increase in 12 cases may occur for 1000 additional unemployed individuals (β = 0.01224). This adds $2598 in direct medical care. Sequalae costs are estimated near $3.5 million with a large cost disparity existing between men and women [9]. This cost should be investigated further with the emergence of multi-drug resistant gonorrhea [10]. This difference in conclusions highlights the need to consider multiple variables when evaluating the future of STIs. There is no single variable that can accurately predict the future change in STIs without fail. Population growth, size, unemployment, and income must all be considered when predicting the future of STI rates. Table 1 shows the percent change in STI rates from 2008 to 2017 while controlling for population change. The change is predominantly positive, meaning that even as the population is increasing, STIs are increasing at faster rates than the population. Generally larger counties, like Jackson or St. Louis county, displayed smaller percent changes. For example, the most prevalent STI, chlamydia, had a 0.15 and 20.13% increase in Jackson and St. Louis county respectively. Smaller counties displayed significantly larger percent increases. For example, chlamydia cases increased   246.54 and 142.05% in Ste. Genevieve and Stone county, respectively. This shows that STIs are a problem for both small and large counties and are growing at disproportionately high rates in some smaller, more rural counties. We continue to see populations moving for various reasons, commonly pursuing higher education in younger aged individuals [15]. Individuals who are moving from one place to the other may lack social support and consistent healthcare during and after the move [14]. Public health professionals should consider developing interventions within vulnerable moving populations.
Based on these data, we suggest the following action steps. First, public health researchers should assess how population-level changes may be related to other communicable diseases in Missouri. Second, a yearly analysis should be conducted by the Missouri Department of Health and Senior Services to understand how population change may be impacting communicable diseases in Missouri and recommendations for clinical interventions should be developed and implemented by delving into the qualitative side of the data. Lastly, clinicians and public health practitioners in areas with growing, changing populations need to screen more patients for STIs, especially those who have recently moved. On the national level, a similar analysis should be conducted to evaluate the effects of population growth, among other variables, on the nation's STI rates.
The data for this study does not allow assessment of immigration or emigration or differences due to births/ deaths, showing a limitation. Population change is a complex variable. Individuals are likely moving within Where AIC is Akaike Information Criterion value, ΔAIC is the change in Akaike Information Criterion value, W i is the Akaike weights value, and R 2 is the correlational coefficient Presents a test of model fitness for all county variables and their ability to predict STI rate changes. This table also presents the best fit models, where the selected variables do the best job at predicting the STI rate change, as indicated in bold print a w i and R 2 were calculated for only those models considered to be of best fit  Additionally, there may be other external variables that influence the relationships that were not accounted for in the methodology. This further shows the need for this analysis to be produced at the national level. This study uses multiple data sets from the state of Missouri. By integrating many datasets, we are able to study how changing populations may impact health outcomes. This allows for a socioeconomic understanding of health outcomes. If healthcare and public health professionals can quantify how populations will increase and change with population change, precision public health can create targeted interventions. This may take place through evaluation and integration of this study or similar studies into Community Health Improvement Plans (CHIPs) which then develops to include intervention plans based off the findings.
This work follows the social epidemiology network, focused around the social capital subset and some neighborhood effects. Direct neighborhood effects from social isolation of a moving population may explain increasing rates of STIs in growing communities with social ties disrupted. Indirect neighborhood effects of increased unemployment may explain the further movement of populations in search of work, with STIs spreading alongside. More research should be done on these possible implications for social theory. Authors of this manuscript plan to conduct further analyzes using additional covariate data to test the relationships among social capital, neighbor effects, and communicable disease. More interventions and research must also be conducted on policies, Community Health Improvement Plans (CHIPs), laws, and economic factors involved in potential prevention methods for STIs. Population-wide plans should be developed and implemented to benefit the community and reduce the health and economic burden of STIs. STIs continue to pose a growing problem across the United States, Midwest region, and the state of Missouri. Prevention and response are of utmost importance as HIV continues to spread and multi-drug resistance in gonorrhea becomes more apparent in the population. Population-level predictors are imperative to understanding STI rate changes and predicting when they may occur so that intervention may be put into place. As populations change in Missouri, due to movement, unemployment rates, or other variables, STIs change with them. Health care and public health providers should respond to moving populations and individuals through screening for STIs and implementing preventative measures. Missouri law and policy makers should develop legislation to better support moving populations and those facing unemployment in order to limit the spread of STIs. Further, legislation should be drafted to prevent unemployment rates from increasing and making preventative measures, like condoms and sexual education, more widespread. This way, the health and wealth of Missourians and United States residents may be bettered.

Conclusion
As population compositions, economic conditions, and prevention efforts change and grow, STI rates change and grow with them. Population size and growth are instrumental in predicting large-scale changes in STIs. Income, unemployment, and poverty rates must also be considered when evaluating STIs in a large population in order to predict future changes and emphasize prevention efforts as populations shift.